The specific aims of this research project are to explore and extend that hypothesis of structure/function relationship in the curare-mimetic postsynaptic neurotoxins from the venoms of both land (elapid) and sea (hydrophid) snakes which was developed in this laboratory after the first three-dimensional structure of one of these toxins, erabutoxin b, had been determined. The amino acid sequences of more than 50 of these single-chain protein neurotoxins have been determined; they show an extensive pattern of sequence homologous expressed as positions of residue invariance and conservative substitution. Toxicities (LD50) usually lie within a very narrow range. The toxins bind to the acetylcholine receptor (AChR) in the postsynaptic membrane. There are two series of toxins; short chain with 60 yields 62 amino acid residues and long-chain with 66, 71 yields 74 amino acid residues. The objective is to establish X-ray crystal structure analysis the validity of our hypothesis that a) the erabutoxin b structure is the stereochemical prototype or model for this whole class of neurotoxins; both long and short series and b) the reactive site in both short and long (mutatis mutandis) is essentially invariant even in deviant toxins of low toxicity with replacements in critical 'functional' residue positions. It is proposed to attempt to characterize differences between the class of postsynaptic neurotoxins and the class of similar short-chain cardiotoxins and cytotoxins found also in snake venoms. Efforts to answer the question, "Is the reactive site as we have described it in vitro, the stereochemical expression of in vivo function?", will be made at this time by studying the stereochemistry of erabutoxin b crystallized under a wide range of conditions.